Modulation of Antimicrobial Host Defense Peptide Gene Expression by Free Fatty Acids

Antimicrobial resistance is a major concern to public health demanding effective alternative strategies to disease control and prevention. Modulation of endogenous host defense peptide (HDP) synthesis has emerged as a promising antibiotic alternative approach. This study investigated a potential synergy between sugars and butyrate in inducing HDP gene expression in chickens. Our results revealed that sugars differentially regulated HDP expression in both gene- and sugar-specific manners in chicken HD11 macrophage cells. Among eight mono- and disaccharides tested, all were potent inducers of avian β-defensin 9 (AvBD9) gene (p<0.05), but only galactose, trehalose, and lactose obviously upregulated cathelicidin-B1 (CATHB1) gene expression. The expression of AvBD14 gene, on the other hand, was minimally influenced by sugars. Moreover, all sugars exhibited a strong synergy with butyrate in enhancing AvBD9 expression, while only galactose, trehalose, and lactose were synergistic with butyrate in CATHB1 induction. No synergy in AvBD14 induction was observed between sugars and butyrate. Although lactose augmented the expression of nearly all HDP genes, its synergy with butyrate was only seen with several, but not all, HDP genes. Mucin-2 gene was also synergistically induced by a combination of lactose and butyrate. Furthermore, lactose synergized with butyrate to induce AvBD9 expression in chicken jejunal explants (p<0.05). Mechanistically, hyper-acetylation of histones was observed in response to both butyrate and lactose, relative to individual compounds. Mitogen-activated protein kinase, NF-κB, and cyclic adenosine monophosphate signaling pathways were also found to be involved in butyrate- and lactose-mediated synergy in AvBD9 induction. Collectively, a combination of butyrate and a sugar with both HDP-inducing and barrier protective activities holds the promise to be developed as an alternative to antibiotics for disease control and prevention.

Download Full-text

Butyrate Enhances Disease Resistance of Chickens by Inducing Antimicrobial Host Defense Peptide Gene Expression

PLoS ONE ◽

10.1371/journal.pone.0027225 ◽

2011 ◽

Vol 6 (11) ◽

pp. e27225 ◽

Cited By ~ 112

Author(s):

Lakshmi T. Sunkara ◽

Mallika Achanta ◽

Nicole B. Schreiber ◽

Yugendar R. Bommineni ◽

Gan Dai ◽

...

Keyword(s):

Gene Expression ◽

Disease Resistance ◽

Host Defense ◽

Host Defense Peptide ◽

Peptide Gene

Download Full-text

Fatty Acid Supplied as Triglyceride Regulates SRE-Mediated Gene Expression as Efficiently as Free Fatty Acids

Lipids ◽

10.1007/s11745-007-3093-x ◽

2007 ◽

Vol 42 (10) ◽

pp. 885-891 ◽

Cited By ~ 6

Author(s):

Narumon Densupsoontorn ◽

Tilla S. Worgall ◽

Toru Seo ◽

Hiroko Hamai ◽

Richard J. Deckelbaum

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Fatty Acid ◽

Free Fatty Acids

Download Full-text

Free Fatty Acids Impair FGF21 Action in HepG2 Cells

Cellular Physiology and Biochemistry ◽

10.1159/000438540 ◽

2015 ◽

Vol 37 (5) ◽

pp. 1767-1778 ◽

Cited By ~ 5

Author(s):

Mohamed Asrih ◽

Christophe Montessuit ◽

Jacques Philippe ◽

François R. Jornayvaz

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Lipid Metabolism ◽

Free Fatty Acids ◽

Hepg2 Cells ◽

Lipid Lowering ◽

Fibroblast Growth Factor 21 ◽

Beneficial Effects ◽

Positive Effects

Background/Aims: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). Methods: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. Results: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. Conclusion: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.

Download Full-text

Free Fatty Acids Repress the GLUT4 Gene Expression in Cardiac Muscle via Novel Response Elements

Journal of Biological Chemistry ◽

10.1074/jbc.m502740200 ◽

2005 ◽

Vol 280 (41) ◽

pp. 34786-34795 ◽

Cited By ~ 59

Author(s):

Michal Armoni ◽

Chava Harel ◽

Fabiana Bar-Yoseph ◽

Simcha Milo ◽

Eddy Karnieli

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Free Fatty Acids ◽

Cardiac Muscle ◽

Response Elements ◽

Glut4 Gene Expression

Download Full-text

Effects of Increased Myocardial Tissue Concentration of Myristic, Palmitic and Palmitoleic Acids on the Course of Cardiac atrophy of the Failing Heart Unloaded by Heterotopic Transplantation

Physiological Research ◽

10.33549/physiolres.933637 ◽

2018 ◽

pp. 13-30 ◽

Cited By ~ 2

Author(s):

M. POKORNÝ ◽

I. MRÁZOVÁ ◽

J. MALÝ ◽

J. PIRK ◽

I. NETUKA ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Tissue Concentration ◽

Heart Tissue ◽

Heart Weight ◽

Chain Gene ◽

Tissue Concentrations ◽

Cardiac Atrophy ◽

Failing Heart ◽

Peptide Gene

The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HTx) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HTx was determined on days 7, 14, 21 and 28 after HTx in recipients of either healthy or failing hearts. HTx of healthy hearts resulted in 23±3, 46±3, 48±4 and 46±4 % HW loss at the four time-points. HTx of the failing heart resulted in even greater HW losses, of 46±4, 58±3, 66±2 and 68±4 %, respectively (P<0.05). Activation of “fetal gene cardiac program” (e.g. beta myosin heavy chain gene expression) and “genes reflecting cardiac remodeling” (e.g. atrial natriuretic peptide gene expression) after HTx was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HTx failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy.

Download Full-text

Effect of Free Fatty Acids on Inflammatory Gene Expression and Hydrogen Peroxide Production by Ex Vivo Blood Mononuclear Cells

Nutrients ◽

10.3390/nu12010146 ◽

2020 ◽

Vol 12 (1) ◽

pp. 146 ◽

Cited By ~ 1

Author(s):

Antoni Sureda ◽

Miquel Martorell ◽

Maria del Mar Bibiloni ◽

Cristina Bouzas ◽

Laura Gallardo-Alfaro ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Free Fatty Acids ◽

Mononuclear Cells ◽

Ex Vivo ◽

H2o2 Production ◽

Inflammatory Gene Expression ◽

Inflammatory Gene ◽

Blood Mononuclear Cells ◽

Docosahexaenoic Acids

The aim of this study was to assess free fatty acids’ (FAs) ex vivo anti-/proinflammatory capabilities and their influence on inflammatory gene expression and H2O2 production by human peripheral blood mononuclear cells (PBMCs). Anthropometric and clinical measurements were performed in 26 participants with metabolic syndrome. Isolated PBMCs were incubated ex vivo for 2 h with several free fatty acids—palmitic, oleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic at 50 μM, and lipopolysaccharide (LPS) alone or in combination. H2O2 production and IL6, NFκB, TLR2, TNFα, and COX-2 gene expressions were determined. Palmitic, γ-linolenic, and arachidonic acids showed minor effects on inflammatory gene expression, whereas oleic, α-linolenic, and docosahexaenoic acids reduced proinflammatory gene expression in LPS-stimulated PBMCs. Arachidonic and α-linolenic acids treatment enhanced LPS-stimulated H2O2 production by PBMCs, while palmitic, oleic, γ-linolenic, and docosahexaenoic acids did not exert significant effects. Oleic, α-linolenic, and docosahexaenoic acids induced anti-inflammatory responses in PBMCs. Arachidonic and α-linolenic acids enhanced the oxidative status of LPS-stimulated PBMCs. In conclusion, PBMC ex vivo assays are useful to assess the anti-/proinflammatory and redox-modulatory effects of fatty acids or other food bioactive compounds.

Download Full-text

Metabolic Effects of Long-Term Reduction in Free Fatty Acids With Acipimox in Obesity: A Randomized Trial

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-3696 ◽

2016 ◽

Vol 101 (3) ◽

pp. 1123-1133 ◽

Cited By ~ 11

Author(s):

Hideo Makimura ◽

Takara L. Stanley ◽

Caroline Suresh ◽

Ana Luisa De Sousa-Coelho ◽

Walter R. Frontera ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Insulin Sensitivity ◽

Free Fatty Acids ◽

Glucose Homeostasis ◽

Mitochondrial Function ◽

Effect Size ◽

Metabolic Effects ◽

Mitochondrial Density

Abstract Context: Increased circulating free fatty acids (FFAs) have been proposed to contribute to insulin resistance in obesity. Short-term studies have investigated the effects of acipimox, an inhibitor of hormone-sensitive lipase, on glucose homeostasis, but longer-term studies have not been performed. Objective: To test the hypothesis that long-term treatment with acipimox would reduce FFA and improve insulin sensitivity among nondiabetic, insulin-resistant, obese subjects. Design, Setting, Patients, and Intervention: At an academic medical center, 39 obese men and women were randomized to acipimox 250 mg thrice-daily vs identical placebo for 6 months. Main Outcome Measures: Plasma lipids, insulin sensitivity, adiponectin, and mitochondrial function via assessment of the rate of post-exercise phosphocreatine recovery on 31P-magnetic resonance spectroscopy as well as muscle mitochondrial density and relevant muscle gene expression. Results: Fasting glucose decreased significantly in acipimox-treated individuals (effect size, −6 mg/dL; P = .02), in parallel with trends for reduced fasting insulin (effect size, −6.8 μU/mL; P = .07) and HOMA-IR (effect size, −1.96; P = .06), and significantly increased adiponectin (effect size, +668 ng/mL; P = .02). Acipimox did not affect insulin-stimulated glucose uptake, as assessed by euglycemic, hyperinsulinemic clamp. Effects on muscle mitochondrial function and density and on relevant gene expression were not seen. Conclusion: These data shed light on the long-term effects of FFA reduction on insulin sensitivity, other metabolic parameters, and muscle mitochondrial function in obesity. Reduced FFA achieved by acipimox improved fasting measures of glucose homeostasis, lipids, and adiponectin but had no effect on mitochondrial function, mitochondrial density, or muscle insulin sensitivity.

Download Full-text